A Thermodynamic Analysis of the Binding Specificity between Four Human PDZ Domains and Eight Host, Viral and Designed Ligands
PDZ domains are binding modules mostly involved in cell signaling and cell–cell junctions. These domains are able to recognize a wide variety of natural targets and, among the PDZ partners, viruses have been discovered to interact with their host via a PDZ domain. With such an array of relevant and...
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doaj-be9a83c697c4472aaae15a027f52c6252021-08-26T13:33:26ZengMDPI AGBiomolecules2218-273X2021-07-01111071107110.3390/biom11081071A Thermodynamic Analysis of the Binding Specificity between Four Human PDZ Domains and Eight Host, Viral and Designed LigandsEva S. Cobos0Ignacio E. Sánchez1Lucía B. Chemes2Jose C. Martinez3Javier Murciano-Calles4Departamento Química Física, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Ciencias, e Instituto de Biotecnología, Universidad de Granada, 18071 Granada, SpainLaboratorio de Fisiología de Proteínas, Facultad de Ciencias Exactas y Naturales, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires, 1428 Buenos Aires, ArgentinaInstituto de Investigaciones Biotecnológicas (IIBiO-CONICET), Universidad Nacional de San Martín, 1650 Buenos Aires, ArgentinaDepartamento Química Física, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Ciencias, e Instituto de Biotecnología, Universidad de Granada, 18071 Granada, SpainDepartamento Química Física, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Ciencias, e Instituto de Biotecnología, Universidad de Granada, 18071 Granada, SpainPDZ domains are binding modules mostly involved in cell signaling and cell–cell junctions. These domains are able to recognize a wide variety of natural targets and, among the PDZ partners, viruses have been discovered to interact with their host via a PDZ domain. With such an array of relevant and diverse interactions, PDZ binding specificity has been thoroughly studied and a traditional classification has grouped PDZ domains in three major specificity classes. In this work, we have selected four human PDZ domains covering the three canonical specificity-class binding mode and a set of their corresponding binders, including host/natural, viral and designed PDZ motifs. Through calorimetric techniques, we have covered the entire cross interactions between the selected PDZ domains and partners. The results indicate a rather basic specificity in each PDZ domain, with two of the domains that bind their cognate and some non-cognate ligands and the two other domains that basically bind their cognate partners. On the other hand, the host partners mostly bind their corresponding PDZ domain and, interestingly, the viral ligands are able to bind most of the studied PDZ domains, even those not previously described. Some viruses may have evolved to use of the ability of the PDZ fold to bind multiple targets, with resulting affinities for the virus–host interactions that are, in some cases, higher than for host–host interactions.https://www.mdpi.com/2218-273X/11/8/1071PDZ domainbinding specificityvirusthermodynamicsisothermal titration calorimetrydifferential scanning calorimetry |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eva S. Cobos Ignacio E. Sánchez Lucía B. Chemes Jose C. Martinez Javier Murciano-Calles |
spellingShingle |
Eva S. Cobos Ignacio E. Sánchez Lucía B. Chemes Jose C. Martinez Javier Murciano-Calles A Thermodynamic Analysis of the Binding Specificity between Four Human PDZ Domains and Eight Host, Viral and Designed Ligands Biomolecules PDZ domain binding specificity virus thermodynamics isothermal titration calorimetry differential scanning calorimetry |
author_facet |
Eva S. Cobos Ignacio E. Sánchez Lucía B. Chemes Jose C. Martinez Javier Murciano-Calles |
author_sort |
Eva S. Cobos |
title |
A Thermodynamic Analysis of the Binding Specificity between Four Human PDZ Domains and Eight Host, Viral and Designed Ligands |
title_short |
A Thermodynamic Analysis of the Binding Specificity between Four Human PDZ Domains and Eight Host, Viral and Designed Ligands |
title_full |
A Thermodynamic Analysis of the Binding Specificity between Four Human PDZ Domains and Eight Host, Viral and Designed Ligands |
title_fullStr |
A Thermodynamic Analysis of the Binding Specificity between Four Human PDZ Domains and Eight Host, Viral and Designed Ligands |
title_full_unstemmed |
A Thermodynamic Analysis of the Binding Specificity between Four Human PDZ Domains and Eight Host, Viral and Designed Ligands |
title_sort |
thermodynamic analysis of the binding specificity between four human pdz domains and eight host, viral and designed ligands |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2021-07-01 |
description |
PDZ domains are binding modules mostly involved in cell signaling and cell–cell junctions. These domains are able to recognize a wide variety of natural targets and, among the PDZ partners, viruses have been discovered to interact with their host via a PDZ domain. With such an array of relevant and diverse interactions, PDZ binding specificity has been thoroughly studied and a traditional classification has grouped PDZ domains in three major specificity classes. In this work, we have selected four human PDZ domains covering the three canonical specificity-class binding mode and a set of their corresponding binders, including host/natural, viral and designed PDZ motifs. Through calorimetric techniques, we have covered the entire cross interactions between the selected PDZ domains and partners. The results indicate a rather basic specificity in each PDZ domain, with two of the domains that bind their cognate and some non-cognate ligands and the two other domains that basically bind their cognate partners. On the other hand, the host partners mostly bind their corresponding PDZ domain and, interestingly, the viral ligands are able to bind most of the studied PDZ domains, even those not previously described. Some viruses may have evolved to use of the ability of the PDZ fold to bind multiple targets, with resulting affinities for the virus–host interactions that are, in some cases, higher than for host–host interactions. |
topic |
PDZ domain binding specificity virus thermodynamics isothermal titration calorimetry differential scanning calorimetry |
url |
https://www.mdpi.com/2218-273X/11/8/1071 |
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